crossing96/oncoscreening huggingface dataset:
ERO1A promotes the proliferation, migration and invasion of bladder cancer through ALOX5 mediated activation of JAK-STAT signaling pathway.	BACKGROUND: Endoplasmic reticulum oxidoreductase 1 A (ERO1A) is a protein disulfide oxidoreductase. ERO1A is involved in the progression of various tumors, but the potential mechanism of its action in bladder cancer remains unclear. METHODS: In this study, we utilized data from public databases to investigate the expression pattern of ERO1A. Through CCK-8, EdU, wound healing, and Transwell invasion assays, we evaluated the effects of ERO1A on the proliferation, migration, and invasion abilities of bladder cancer cells. We further explored the specific molecular mechanism of ERO1A. Finally, a subcutaneous tumor formation model in nude mice was established to detect the function of ERO1A in vivo. RESULTS: Silencing the expression of ERO1A inhibits the proliferation, migration and invasion of bladder cancer cells, and also suppresses tumor growth in vivo. Mechanistically, ERO1A binds to and suppresses the phosphorylation of ALOX5, which in turn activates the JAK-STAT signaling pathway and subsequently suppresses autophagy. CONCLUSION: In conclusion, this study demonstrates that ERO1A could promote the proliferation, migration, and invasion of bladder cancer cells by regulating the ALOX5/JAK/STAT/autophagy signaling axis. ERO1A may serve as a novel molecular marker for the diagnosis and treatment of clinical bladder cancer patients.	bladder
Baicalin inhibits bladder cancer progression by suppressing PD-L1-mediated M2 macrophage polarization via ALDH2.	This study aims to elucidate the anti-tumor mechanism of baicalin in bladder cancer (BCa), with a focus on the role of baicalin in tumor-associated macrophage polarization. BCa-related differentially expressed genes (DEGs) were detected using the GSE13507 dataset and intersected with predicted targets of baicalin to screen for core targets. Aldehyde dehydrogenase 2 (ALDH2) expression was assessed by RT-qPCR and Western blotting. An ALDH2-knockdown cell line was established for co-culture with bone marrow-derived macrophages (BMDMs) to evaluate macrophage polarization. Cellular behaviors were assessed respectively. An in vivo xenograft mouse model was used to validate the anti-tumor effects of baicalin. ALDH2 was downregulated in BCa. Baicalin directly bound to and upregulated ALDH2 expression. Elevated ALDH2 downregulated programmed death-ligand 1 (PD-L1) and promoted M1 macrophage polarization, thereby enhancing anti-tumor immune responses. Baicalin significantly inhibited the malignant phenotypes of BCa cells and reduced tumor growth in xenograft models. Notably, the anti-tumor effects of baicalin were partially reversed by ALDH2 knockdown or PD-L1 inhibition. Baicalin exerts potent anti-tumor effects in BCa by upregulating ALDH2, thereby suppressing PD-L1-mediated M2 macrophage polarization and remodeling the tumor immune microenvironment. This mechanism provides a novel therapeutic strategy for combating BCa progression.	bladder
Clinical characteristics of the ALK fusion-positive bladder PMP and efficacy of lorlatinib: a two-case report and literature review.	Pseudosarcomatous myofibroblastic proliferation (PMP) is a rare anaplastic lymphoma kinase (ALK), ALK fusion-associated tumor-like lesion that requires differentiation from inflammatory myofibroblastic tumor (IMT). This article reports two cases of bladder ALK fusion-positive PMP: a 16-year-old male achieved partial remission (PR) postoperatively with lorlatinib but experienced memory decline and mood disturbances, which resolved after dose reduction; a 34-year-old female showed significant tumor shrinkage (PR) without severe adverse reactions. The study confirms the marked efficacy of ALK inhibitors in ALK-positive PMP, but highlights the need to monitor neurotoxicity in adolescent patients. Through analysis of the FN1 (Fibronectin 1)-ALK fusion mechanism and literature review, this study emphasizes the importance of pathological differentiation, individualized treatment, and dynamic cognitive monitoring, providing insights for precision therapy in rare diseases.	bladder
The staging of re-TURB is crucial in predicting the response to BCG therapy in patients with T1 high-grade bladder cancer.	PURPOSE: This study aimed to evaluate whether the pathological findings from repeat transurethral resection of bladder (re-TURB) predict Bacillus Calmette-Guérin (BCG) response in patients with T1 high-grade bladder cancer. MATERIALS AND METHODS: We analyzed patients with bladder cancer enrolled in the prospective patient registry system of Seoul National University, SUPER-UC, from March 2016 to May 2022. Patients with T1 high-grade cancer who underwent re-TURB and BCG instillation were identified. Re-TURB pathology and its relationship with BCG response were analyzed. RESULTS: Out of a total of 2,673 patients with bladder cancer, 539 had T1 high-grade bladder cancer. Among these, 251 patients underwent subsequent re-TURB and BCG instillation. Of the 251 patients, 210 (83.7%) were male, and TURB was performed as the initial procedure in 232 cases (92.4%). In the TURB specimens of T1 high-grade cancer, concomitant carcinoma in situ (CIS), lymphovascular invasion, and variant histology were observed in 27 (10.8%), 54 (21.5%), and 29 (11.6%) cases, respectively. However, these factors were not associated with BCG failure after re-TURB. Re-TURB pathology showed chronic inflammation (51.8%), CIS (17.5%), Ta (15.5%), and T1 (15.1%). These findings were significantly correlated with BCG responsiveness. Notably, BCG failure was reported in 20.8% of patients with chronic inflammation, which showed the best response, compared to patients with T1 pathology, where BCG failure was observed in 47.4% of cases (p=0.011). CONCLUSIONS: The pathological results of re-TURB play a critical role in determining the BCG response in patients with T1 high-grade bladder cancer.	bladder
Utilization of intravesical chemotherapy following TURBT: A pre-implementation analysis of American College of Surgeon Commission on Cancer GU quality measures.	OBJECTIVE: To evaluate utilization trends of postoperative intravesical chemotherapy (IVC) following transurethral resection of bladder tumor (TURBT) in patients with low-grade Ta non-muscle invasive bladder cancer (NMIBC) prior to implementation of a new Commission on Cancer (CoC) quality measure, and to identify factors influencing adherence in order to refine strategies for improving compliance. METHODS: Patients aged 18 years and older who underwent TURBT (2018-2020) were identified from the National Cancer Database (NCDB). Only those with low-grade Ta urothelial carcinoma were included. Patients with high-grade disease, advanced-stage NMIBC, or variant histology were excluded. The primary outcome was postoperative IVC utilization. Clinical and demographic variables analyzed included age, sex, race/ethnicity, insurance, tumor size, comorbidities, facility type, and geographic region. A multivariable logistic regression identified predictors of adherence. RESULTS: Among 25,518 patients, 21.8% received IVC, increasing from 20.84% (2018) to 23.09% (2020) (P = 0.0024). Younger age, smaller tumors, non-Black/non-White race, treatment at integrated network cancer programs, urban residence, and lower income were associated with higher IVC use. Medicaid/Medicare coverage correlated with lower utilization. CONCLUSIONS: Significant disparities exist in IVC adherence. Addressing sociodemographic barriers, improving institutional compliance, and overcoming implementation challenges are essential to optimizing patient outcomes. The CoC quality measure may improve adherence and standardize care delivery.	bladder
Causal relationships between immune cells and common urinary system tumors: A bidirectional analysis of Mendelian randomization.	We conducted research on the causal relationships between human immune cells and common urinary system tumors. This study conducted 2-sample Mendelian randomization analyses to determine the causal relationships between immune cell traits and the risk of kidney, bladder, and prostate cancers (PCs). Sensitivity analyses were used to validate the robustness of the results, focusing on pleiotropy and heterogeneity. These findings may inform early diagnosis and personalized immunotherapy for urinary system tumors. Our study identified 12 immune cell phenotypes associated with kidney cancer, including CD127- CD8br absolute cell (AC; odds ratio [OR] = 1.205, 95% confidence interval [CI]: 1.099-1.320, P = 6.73 × 10-5); CD25 on CD39+ activated regulatory T cell (OR = 1.136, 95% CI: 1.037-1.244, P = .006); CD4 on TD CD4+ (OR = 1.102, 95% CI: 1.027-1.182, P = .007); immunoglobulin D (IgD)+ CD38-% lymphocyte (OR = 1.101, 95% CI: 1.031-1.177, P = .004); CD20 on IgD- CD38br (OR = 1.067, 95% CI: 1.017-1.120, P = .008); CD25 on B cell (OR = 1.067, 95% CI: 1.022-1.114, P = .004); HLA DR on B cell (OR = 0.929, 95% CI: 0.882-0.979, P = .006); HLA DR on CD33dim HLA DR+ CD11b- (OR = 0.924, 95% CI: 0.874-0.977, P = .005); HLA DR on CD14+ CD16+ monocyte (OR = 0.947, 95% CI: 0.916-0.980, P = .002); CD62L- plasmacytoid DC %DC (OR = 0.906, 95% CI: 0.850-0.965, P = .002); CD11c on myeloid DC (OR = 0.904, 95% CI: 0.853-0.959, P = 7.38 × 10-4); CD11c on CD62L+ myeloid DC (OR = 0.930, 95% CI: 0.881-0.981, P = .008). Four immune cell phenotypes were associated with bladder cancer, including CD38dim% lymphocyte (OR = 1.081, 95% CI: 1.020-1.145, P = .009); HLA DR+ CD8br AC (OR = 0.940, 95% CI: 0.897-0.985, P = .009); IgD on unsw mem (OR = 0.908, 95% CI: 0.856-0.963, P = .001). In the conventional dendritic cell group, FSC-A on granulocyte (OR = 0.897, 95% CI: 0.836-0.963, P = .003). Six immune cell phenotypes were associated with PC, including CD19 on IgD- CD38- (OR = 1.080, 95% CI: 1.033-1.129, P = 6.21 × 10-4); CD27 on CD20- (OR = 1.040, 95% CI: 1.010-1.072, P = .009); CD86+ plasmacytoid DC %DC (OR = 1.053, 95% CI: 1.013-1.094, P = .009); CD25 on IgD+ CD38- (OR = 0.974, 95% CI: 0.960-0.988, P = 2.59 × 10-4); CD25hi CD45RA+ CD4 not regulatory T cell AC (OR = 0.962, 95% CI: 0.937-0.989, P = .006); CD127 on CD28- CD8br (OR = 0.952, 95% CI: 0.920-0.984, P = .004). Our study, utilizing Mendelian randomization genetic methods, has demonstrated the causal associations between immune cell phenotypes and kidney cancer, bladder cancer, and PC, providing guidance for future clinical diagnosis and treatment of these 3 malignant tumors of the urinary system.	bladder
Immunohistochemistry-Based Molecular Profiling of Muscle-Invasive Bladder Cancer: Analysis of 100 Consecutive Cases with Morphological Correlation.	Background/Objectives: This study aimed to profile the molecular variants of muscle-invasive bladder cancer (MIBC) based on immunohistochemical analysis and to make a correlation with morphological characteristics in a series of 100 consecutive patients. Methods: A retrospective single-center study was conducted on 100 consecutive cases of MIBC (2021-2024). A selected immunohistochemical (IHC) panel (including CK5/6, CK20, and p16) was applied in all cases to classify the tumors into known molecular variants (luminal papillary, luminal non-specified, luminal unstable, stroma-rich, basal/squamous, neuroendocrine-like). Results: Seven molecular subtypes are identified: basal (33%), luminal papillary (24%), luminal unstable (16%), luminal non-specified (10%), basoluminal (double-positive) (9%), neuroendocrine-like (double-negative with neuroendocrine morphology) (6%), and stroma-rich (2%). This distribution largely matches published data (Consensus Classification and The Cancer Genome Atlas (TCGA)), with minor differences (e.g., a lower share of the stroma-rich variant). A strong correlation is found between the histological subtypes of some tumors and their molecular variant (χ(2), p < 0.001): for example, all cases of urothelial carcinoma with squamous differentiation are basal, micropapillary tumors are entirely luminal, and small-cell carcinomas are neuroendocrine-like. Conclusions: The results demonstrate that the morphological subtype of urothelial carcinoma largely predetermines the molecular profile. Combining classic histopathology with IHC-based profiling allows for a more complete characterization of the tumor and aids prognosis and personalized treatment in MIBC.	bladder
Exploring the influence of the bladder microbiome on BCG immunotherapy outcomes for high-risk non muscle invasive bladder cancer.	BACKGROUND: Intravesical Bacillus Calmette-Guérin (BCG) is an established adjuvant therapy for high-risk superficial bladder cancer, though its efficacy varies among patients. Recent interest in the urinary microbiome comprising microorganisms inhabiting the urinary tract stems from its potential impact on various urological conditions, including bladder cancer. Our study investigates the possible relationship between the bladder microbiome and BCG therapy outcomes in a preliminary and explorative analysis. METHODS: We conducted a retrospective, descriptive study involving 31 high-risk bladder cancer (BC) patients treated with BCG. BC tissues were collected pre-treatment, and formalin-fixed paraffin-embedded (FFPE) samples were analyzed. DNA extracted from these samples underwent high-throughput 16S rRNA amplicon sequencing targeting the V1-V3 regions. RESULTS: Our cohort consisted of 15 BCG-resistant patients and 16 responders. Median instillation numbers were six (IQR: 6-9) for resistant patients and twelve (IQR: 14-15) for responders, with a median follow-up length of six months (IQR: 3.3-9.5) and 43 months (IQR: 24-55), respectively. Significant differences were observed in the microbiome: BCG responders showed higher median percentages of Firmicutes (1.1 vs. 0.3, P=0.0293) and Verrucomicrobiota (0.9 vs. 0.1, P=0.0285). Additionally, Fusobacteriota was more prevalent among responders (75% vs. 33.3%, P=0.0198), while Cyanobacteria were more common in resistant patients (73.3% vs. 31.3%, P=0.0191). CONCLUSIONS: Our preliminary findings illuminate the bladder microbiome's role in influencing BCG therapy outcomes, underscoring the complex microbial interplay affecting treatment efficacy in urological diseases. This explorative study sets the groundwork for ongoing data collection and future research pathways aimed at further delineating these relationships.	bladder
Urease-Powered Nanomotors for Enhanced Mucosal and Tumor Penetration To Augment Sonodynamic Therapy in Bladder Cancer.	Sonodynamic therapy (SDT) represents a promising minimally invasive approach for treating bladder cancer, however, its efficacy following intravesical instillation is substantially compromised by the glycosaminoglycan-rich mucosal barrier and the cyclic voiding process of the bladder. To address these limitations, nanomotors coloaded with enzyme and sonosensitizer were engineered to enhance self-propelled tissue penetration and prolong retention of SDT for bladder cancer. Herein, urine-derived exosomes (EXO) were isolated using density gradient ultracentrifugation and subsequently engineered into EXO@UT nanovesicles (NVs) via electroporation-mediated coencapsulation of urease and tetrakis (4-carboxyphenyl) porphyrin. The NVs catalyze the decomposition of urea within the bladder to generate carbon dioxide and ammonia, thereby propelling their migration toward the bladder mucosa and circumventing washout during micturition as well as enhanced retention within tumor. Following intravesical administration in mice bearing bladder cancer, the NVs with self-propulsion demonstrated significantly enhanced infiltration into mucosal tissues and improved drug accumulation at the tumor site, compared to static counterpart which remained largely localized on the mucosal surface. The self-propelled NVs for SDT activated by low-intensity ultrasound irradiation demonstrated significantly stronger tumor growth suppression and extended animal survival compared to those exposed to external near-infrared illumination. Thus, this study presents a robust therapeutic platform based on self-propelled NVs that effectively overcome mucosal barriers and potentiate SDT, offering a promising strategy for enhanced treatment of bladder cancer.	bladder
Paris polyphylla Smith var. yunnanensis-derived saponins potentiate the antitumor activity of GPX4 inhibitors.	ETHNOPHARMACOLOGICAL RELEVANCE: Paris polyphylla Smith var. yunnanensis (Franch.) Hand.-Mazz. is a well-known medicinal herb valued in traditional medicine for its antitumor properties. Its primary bioactive constituents, saponins, exert anti-bladder cancer effects by suppressing lipid metabolism. However, whether these saponins enhance the antitumor efficacy of glutathione peroxidase 4 (GPX4) inhibitors remains unexplored. AIM OF THE STUDY: This study aimed to investigate whether the total saponins of P. polyphylla var. yunnanensis (PPT) and its constituent polyphyllin VII (PPVII) inhibit the Akt-SREBP1 signaling axis and potentiate the antiproliferative activity of the GPX4 inhibitor JKE-1674 (JKE) across multiple cancer types. MATERIALS AND METHODS: The binding of PPVII to growth factor receptor binding protein 2 (GRB2) was assessed using site-directed mutagenesis and surface plasmon resonance. Antitumor activity was evaluated through in vitro assays (cell viability, apoptosis, lipid ROS, Western blotting, colony formation) in various cancer cell lines treated with PPT or PPVII, alone or in combination with JKE. Synergistic antitumor effects were confirmed in vivo using bladder cancer xenograft models. To assess the clinical relevance of our targets, we analyzed data from public databases (UALCAN, TIMER3, The Human Protein Atlas) to correlate their expression levels with patient prognosis. RESULTS: Molecular interaction studies revealed that PPVII binds to GRB2 by targeting a critical clamp-like structure formed by residues ILE65, GLN157, TYR160, and PHE182. While the I65A mutation significantly reduced binding, the combined Q157A/Y160A/F182A mutation had a profoundly greater disruptive effect. Functionally, GRB2 inhibition suppressed the growth of chemoresistant bladder cancer cells and enhanced gemcitabine sensitivity. Both PPT and PPVII suppressed the Akt-SREBP1 pathway and cell proliferation in bladder, breast, and liver cancer models. Notably, PPT and PPVII dramatically potentiated the cytotoxicity of JKE. The JKE/PPVII combination synergistically induced oxidative stress-driven lipid peroxidation, endoplasmic reticulum stress, MAPK pathway activation, and apoptosis in vitro, and exhibited potent antitumor efficacy in vivo. Bioinformatics confirmed GRB2 and GPX4 co-expression in liver cancer, and the PPVII/JKE combination effectively suppressed LIHC cell proliferation. CONCLUSION: This study validates GRB2 as a promising therapeutic target. P. polyphylla var. yunnanensis-derived saponins (PPT and PPVII) inhibit GRB2-mediated Akt-SREBP1 pathway activation in bladder, breast, and liver cancer. Furthermore, combining PPVII with the GPX4 inhibitor JKE represents a novel, synergistic cancer therapy strategy, acting through a mechanism that involves ROS-dependent activation of multiple cell death pathways.	bladder
CKS2 promotes the malignant phenotypes of bladder cancer cells via PI3K/AKT signaling pathway activation.	Cyclin-dependent kinase subunit 2 (CKS2) has been implicated in various malignancies. This study investigates the mechanism by which CKS2 contributes to bladder cancer (BC) progression. Abnormally expressed genes were identified by differential analysis of tumor and normal tissues using Gene Expression Omnibus datasets. Subsequently, functional assays - including cell proliferation, Transwell migration, colony formation, wound healing, flow cytometry, and enzyme-linked immunosorbent assays - were performed to provide cellular evidence supporting the oncogenic function of CKS2 in BC. The results demonstrated significantly elevated CKS2 expression in BC cells than in normal urothelial cells. CKS2 overexpression promoted cell proliferation, cell migration and invasion. Mechanistically, CKS2 overexpression caused a marked reduction in PTEN protein levels, thereby inhibiting PIP3 degradation and indirectly activating the PI3K/AKT signaling pathway. Furthermore, CKS2 promoted phosphorylation and degradation of p27 Kip1 (Thr187), consequently contributing to cell cycle deregulation and further enhancing PI3K/AKT pathway activity. In contrast, CKS2 knockdown produced the opposite effects. Notably, treatment with the PI3K inhibitor LY294002 effectively reversed CKS2-induced BC cell proliferation and metastasis. In conclusion, CKS2 promoted the malignant phenotypes of BC cells by enhancing PI3K/AKT pathway activity through dual mechanisms involving PTEN downregulation and p27 Kip1-mediated cell cycle dysregulation.	bladder
E-ABIN: an explainable module for anomaly detection in biological networks.	The increasing availability of large-scale omics data calls for robust analytical frameworks capable of handling complex gene expression datasets while offering interpretable results. Recent advances in artificial intelligence have enabled the identification of aberrant molecular patterns distinguishing disease states from healthy controls. Coupled with improvements in model interpretability, these tools now support the identification of genes potentially driving disease phenotypes. However, current approaches to gene anomaly detection often remain limited to single datasets and lack accessible graphical interfaces. We introduce E-ABIN, a general-purpose, explainable framework for anomaly detection in biological networks. E-ABIN combines classical machine learning and graph-based deep learning techniques within a unified, user-friendly platform, enabling the detection and interpretation of anomalies from gene expression or methylation-derived networks. By integrating algorithms such as support vector machines, random forests, graph autoencoders, and graph adversarial attributed networks, E-ABIN ensures high predictive accuracy while maintaining interpretability. We demonstrate the utility of E-ABIN through case studies of bladder cancer and celiac disease, where it effectively uncovers biologically relevant anomalies and offers insights into disease mechanisms. E-ABIN is freely available on the Zenodo platform at https://doi.org/10.5281/zenodo.17062501.	bladder
Ex Vivo Optical Coherence Tomography Analysis of Resected Human Bladder with a Forward-Looking Microelectromechanical Systems Mirror-Based Catheter.	A technique that enables real-time diagnosis of bladder cancer is needed. Optical coherence tomography (OCT) is a promising technique, but a forward-looking OCT catheter is necessary for OCT to enable bladder cancer diagnosis. This study aims to describe the design of a novel forward-looking microelectromechanical systems (MEMS)-based OCT catheter, assess the performance characteristics, and evaluate its ability to identify histopathological characteristics of bladder specimens. A description of the OCT catheter and systems used is provided. Performance characteristics were measured with a beam profiler and microscopy slide (mirror for dispersion and thickness for lateral calibration). Ex vivo measurements were performed on resected bladder tissue from patients undergoing a radical cystectomy. A forward-looking OCT probe with an outer diameter of 2.52 mm and a rigid length of 17 mm was designed and evaluated. The focus position was measured as 10.9 mm from the MEMS mirror, with a Rayleigh length of 2.55 mm. Several histopathological features could be correlated to OCT features of the ex vivo measurements. In conclusion, a forward-looking OCT probe that can be inserted in the working channel of a rigid cystoscope was designed and evaluated. Performance characteristics were overall in line with simulated expectations.	bladder